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Description

CA-125 is a high-molecular-weight protein antigen that is commonly elevated in patients with known ovarian cancer. CA-125 may also be elevated in other gynecologic malignancies, such as endometrial cancer, although the association is not as consistent as that with ovarian cancer. CA-125 has been widely used as a technique to monitor patients with known ovarian cancer or other gynecologic malignancies that, in individual patients, are associated with elevated levels of CA-125. Frequently, a rising CA-125 will be the initial sign of recurrent disease.

CA-125 has also been investigated as a possible screening tool for ovarian cancer, both in the general population and in patients considered at high risk of ovarian cancer.

Levels of CA-125 may also be elevated in nonmalignant conditions, including pregnancy, endometriosis, pelvic inflammatory disease, benign ovarian masses, and without any identifiable cause.

Policy

Measurements of CA-125 may be considered medically necessary in patients with symptoms suggestive of ovarian cancer or in those with known ovarian cancer.

Measurement of CA-125 may be considered medically necessary in individual patients with other gynecologic malignancies, such as endometrial cancer, in whom baseline levels of CA-125 have been shown to be elevated.

Measurement of CA-125 is considered investigational in asymptomatic patients as a screening technique for ovarian cancer.

Policy Guidelines

Prior to 2001, the non-specific CPT code 86316 was used to describe CA-125. In 2001, a separate CPT code was introduced that explicitly described CA-125. (CPT code 86304: Immunoassay for tumor antigen, quantitative; CA-125)

Benefit Application

BlueCard/National Account Issues

Coverage eligibility of CA-125 as a screening technique for ovarian cancer may be additionally limited by contractual exclusions for screening services.

Rationale

CA-125 for Monitoring and Surveillance of Known Ovarian Cancer and Other Gynecologic CancersThe use of CA-125 to monitor ovarian cancer recurrence in patients with known ovarian cancer is considered standard practice and is not further discussed. In addition, other gynecologic malignancies, particularly endometrial cancer, may also be associated with CA-125 in individual cases. If so, levels of CA-125 may be similarly monitored for cancer recurrence.

CA-125 as a Screening Tool for Ovarian CancerMost ovarian cancers present in an advanced stage such that complete surgical resection is not possible. Therefore, there has been long-standing interest in developing screening techniques for ovarian cancer. Measurements of CA-125 and transvaginal ultrasound have been the techniques most commonly investigated. Validation of any oncologic screening technique requires data showing that the screening is a sensitive and relatively specific technique to identify cancers early in the course of the disease, such that prompt treatment results in an improved outcome. The largest study published to date included 22,000 postmenopausal women. After the initial baseline screening with CA-125, half the women were randomly selected to receive 3 more annual tests, while the other half received no further tests but were followed up by researchers. (1) In the group assigned to receive annual screening, 468 women had elevated CA-125 levels, and 29 were ultimately referred for a surgical biopsy. Of those referred for biopsy, 6 were diagnosed with ovarian cancer, while the other 23 had false-positive results. Ten more women in the screening group developed ovarian cancer during the 8 years they were followed up by the researchers. The high false positive rate and subsequent low positive predictive value indicate that many patients will unnecessarily undergo invasive procedures (laparoscopy or laparotomy) to rule out malignancy. In addition, there is inadequate evidence that screening reduces the morbidity and mortality of ovarian cancer. At the present time, the American Cancer Society (2) and the U.S. Preventive Services Task Force (3) recommend against ovarian cancer screening for average risk women.

Patients with BRCA mutations, or patients with a strong family history of ovarian cancer, are considered at higher risk of ovarian cancer. For example, in patients with a BRCA1 mutation, the risk of ovarian cancer is estimated at 26% by age 76. For those with BRCA2 mutations, the risk is lower, estimated at 10% by age 70. Similarly, the risk associated with a family history will vary according to the number of affected relatives. Some have suggested that CA-125 screening may be appropriate in this high-risk subset of patients. For example, in 1997, the Cancer Genetic Studies Consortium developed recommendations for the follow-up care of individuals with BRCA1 and BRCA2 mutations. (4) These recommendations included annual or semi-annual measurements of CA-125 and transvaginal ultrasound, similar to the recommendations from the American Cancer Society. However, the Cancer Genetics Studies Consortium acknowledges that this screening method was based on expert opinion only with no demonstrated benefit as yet.

2003-5 UpdateUpdated reviews of the peer-reviewed literature on MEDLINE found no clinical trials to support the use of CA-125 screening for ovarian cancer in aymptomatic, low- to average-risk women. In addition, a December 2002 Committee Opinion of the American College of Obstetricians and Gynecologists notes currently available screening tests, including CA-125, do not appear to be beneficial for screening low-risk, asymptomatic women for ovarian cancer. (5) Therefore, the policy statement is unchanged.

The American College of Obstetricians and Gynecologists. ACOG Committee Opinion: number 280, December 2002. The role of the generalist obstetrician-gynecologist in the early detection of ovarian cancer. Obstet Gynecol 2002 Dec; 100(6):1413-6.

Codes

Number

Description

CPT

86304

Immunoassay for tumor antigen, quantitative; CA-125

ICD-9 Procedure

ICD-9 Diagnosis

182

Malignant neoplasm of uterus

183

Malignant neoplasm of ovary and other uterine adnexa

V10.3

Personal history of neoplasm of breast

V16.41

Family history of malignant neoplasm of ovary

HCPCS

Type of Service

Medicine/Oncology

Place of Service

Laboratory

Index

CA-125Ovarian Cancer, CA-125Screening, Ovarian Cancer, CA-125

Policy History

Date

Action

Reason

08/15/01

Add to Medicine section

New policy

04/29/03

Replace policy

Policy updated with literature review for the period of 2001 through February 2003. Policy statement unchanged; references added

03/15/05

Replace Policy

Literature review update for the period of January 2003 through January 2005; updated USPSTF and ACS references. Policy statement unchanged